Oral mucosa and skin show marked regional variation in structure which appears to be related to regional differences in function. Epithelia are continuously regenerating structures and there is evidence to suggest that the connective tissues beneath the epithelium continue, throughout life, to exert directive and permissive influences which maintain normal growth and the regional specificity of structure of epithelia. Many of the adverse pathological processes occurring in the oral cavity, ranging from periodontal disease to carcinoma are associated with, or are casually related to, changes in the maintenance of epithelial structure. Information which leads to findings indicate that (a) epithelial histodifferentiation (as characterized by patterns of keratin synthesis, rates of cell division and establishment of tissue architecture) can be directed by subepithelial connective tissue and (b) that in order to express their intrinsic phenotype, adult epithelia require permissive influences provided by subepithelial, but not deep, connective tissue. The objectives of the proposed reseach are (a) to use standardized in vitro conditions for analyzing the influence of permissive and directive connective tissue effects on epithelia, (b) to examine the ability of neonatal and transformed cells to induce functional changes in connective tissue, (c) to re-examine epithelial migration and differentiation in relation to concepts of dermal permissiveness, and (d) to examine the structural stability of the gingival sulcus in relation to epithelial-mesenchymal interactions. These problems will be investigated using murine and human mucosal and epidermal specimens, either in vitro or transplanted to histocompatible or immunodeficient mice. Specimens will be analyzed by biochemical, ultrastructural, immunofluorescent, and cell kinetic techniques.